A novel regulatory mechanism for a novel phase-variable outer membrane protein of Escherichia coli

Antigen 43 (Ag43) is a prominent hetero-oligomeric protein complex in the outer membrane of Escherichia coli. It is composed of two subunits. alpha 43 (M(r) 60, 000) and beta 43 (M(r) 53, 000) in 1:1 stoichiometry. alpha 43 is surface expressed, extends beyond the O-side chains of smooth lipopolysaccharide and is bound to the cell surface through an interaction with beta 43, itself an integral outer membrane protein, alpha 43 shows limited sequence homology with some enterobacterial adhesins. Expression of Ag43 is subject to reversible phase variation, the rates of variation from the Ag43+ve to Ag43-ve states in liquid minimal medium being approximately 2.2 x 10(-3), the corresponding rates from Ag43-ve to Ag43+ve states being approximately 1 x 10(-3). Phase switching of genes encoding Ag43 are transcriptionally regulated by DNA methylation (deoxyadenosine methylase [dam] mutants being "locked OFF") and by OxyR (oxyR mutants being "locked ON"). It is proposed that OxyR acts as a repressor of Ag43 transcription by binding to unmethylated GATC sites in the regulatory region of the gene. Sequencing and mapping has identified Ag43 as the likely product of the metastable flu gene first described in 1980 by Diderichsen and responsible for colony form variation in E. coli.